论文标题
建模和机械扰动揭示了在空间调节的锚固如何产生哺乳动物纺锤体的空间不同的力学
Modeling and mechanical perturbations reveal how spatially regulated anchorage gives rise to spatially distinct mechanics across the mammalian spindle
论文作者
论文摘要
在细胞分裂期间,纺锤会产生动力移动染色体。在哺乳动物中,微管束称为动脉底纤维(K-纤维),附着并隔离染色体。为此,必须将K纤维牢固地固定在动态主轴上。我们以前开发了微对齐的操作,以机械挑战K纤维锚固,并观察到在空间上不同的响应特征,这些特征揭示了存在异质锚定的存在(Suresh等,2020)。如何精确地在空间上调节锚固,以及哪些力是必要的,足以概括K纤维对力的反应,尚不清楚。在这里,我们开发了一个粗粒的K纤维模型,并结合使用形状分析来推断基础锚固的操纵实验。通过系统地测试不同的锚固方案,我们发现仅在K纤维端处的力就足以概括未经操纵的K纤维形状,但没有操纵的力,而操纵的力也不是在3 $μ$ M长度上的侧面锚定在染色体附近的横向锚固也是必不可少的。这样的锚固稳健地保留了染色体附近的K纤维取向,同时允许在极点周围旋转。较短长度的锚固不能牢固地限制在染色体附近的旋转,而整个纺锤体的锚固会阻塞旋转的极点。总之,这项工作揭示了在空间调节的锚固中如何产生哺乳动物纺锤体中空间不同的力学,我们建议这是功能的关键。
During cell division, the spindle generates force to move chromosomes. In mammals, microtubule bundles called kinetochore-fibers (k-fibers) attach to and segregate chromosomes. To do so, k-fibers must be robustly anchored to the dynamic spindle. We previously developed microneedle manipulation to mechanically challenge k-fiber anchorage, and observed spatially distinct response features revealing the presence of heterogeneous anchorage (Suresh et al. 2020). How anchorage is precisely spatially regulated, and what forces are necessary and sufficient to recapitulate the k-fiber's response to force remain unclear. Here, we develop a coarse-grained k-fiber model and combine with manipulation experiments to infer underlying anchorage using shape analysis. By systematically testing different anchorage schemes, we find that forces solely at k-fiber ends are sufficient to recapitulate unmanipulated k-fiber shapes, but not manipulated ones for which lateral anchorage over a 3 $μ$m length scale near chromosomes is also essential. Such anchorage robustly preserves k-fiber orientation near chromosomes while allowing pivoting around poles. Anchorage over a shorter length scale cannot robustly restrict pivoting near chromosomes, while anchorage throughout the spindle obstructs pivoting at poles. Together, this work reveals how spatially regulated anchorage gives rise to spatially distinct mechanics in the mammalian spindle, which we propose are key for function.